Control of B cell lymphoma recognition via natural killer inhibitory receptors implies a role for human Vgamma9/Vdelta2 T cells in tumor immunity.
The Vgamma9/Vdelta2 T cell receptor (TCR) is expressed by most human gammadelta T cells. We show here that cytotoxic T lymphocytes of the Vgamma9/Vdelta2 subset, but not of the Vdelta1 subset of human gammadelta T cells, express natural killer inhibitory receptors (KIR) with specificity for different HLA class I alleles that down-regulate TCR-mediated signaling in response to HLA class I-expressing B cell lymphomas. Vgamma9/Vdelta2 T cell clones with a T helper cell phenotype lack KIR and produce lymphokines in response to most human B cell lymphomas, just as they do upon recognition of the HLA class I-deficient human Burkitt's lymphoma Daudi. Thus, human Vgamma9/Vdelta2 T cells have an innate specificity for nonpolymorphic cell surface structures expressed by many lymphoma cells and their cytotoxic activity is controlled by KIR. These results imply a general role of human Vgamma9/Vdelta2 T cells in the defense against hematopoietic tumors that is distinct from NK cells.
Fisch
P
P
Department of Immunology, University of Tübingen, Germany.
Meuer
E
E
Pende
D
D
Rothenfusser
S
S
Viale
O
O
Kock
S
S
Ferrone
S
S
Fradelizi
D
D
Klein
G
G
Moretta
L
L
Rammensee
H G
HG
Boon
T
T
Coulie
P
P
van der Bruggen
P
P
D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic